RESUMEN
Recently, we reported that PrP(Sc), a surrogate marker for prion disease, is associated with the cellular fraction of blood from scrapie-infected sheep using a ligand-based immunoassay. In the study reported here, we found that a subset of peripheral blood mononuclear cells is most likely to sequester PrP(Sc) during both the preclinical phase of disease and at clinical end point. These cells had a cell surface phenotype of MHC class II DQ(+), surface immunoglobulin(+), CD11b(+), CD11c(+), CD21(+/)(-), which is consistent with a subpopulation of B cells. What role these cells play in the pathogenesis of scrapie is unclear, but they may contribute to the trafficking of prions to the spleen during early pathogenesis of the disease. Furthermore, tests for preclinical diagnostics could be further improved by targeting these cells.
Asunto(s)
Linfocitos B/metabolismo , Proteínas PrPSc/sangre , Scrapie/sangre , Animales , Biomarcadores , Regulación de la Expresión Génica , Genes MHC Clase II/genética , Genes MHC Clase II/fisiología , OvinosRESUMEN
Milk specimens were collected from lactating cows that had previously been challenged with bovine spongiform encephalopathy (BSE)-infected brain at 4-6 months of age. One group of 10 animals received a single oral dose of 100 g, a second group received 1 g and the third was made up of unexposed controls. The cows were inseminated artificially, and calved at approximately 2 years of age and annually thereafter. Milking was done within the first week following calving and at 10-weekly intervals during the lactation period. Specimens were centrifuged to obtain a fraction enriched for somatic cells and these fractions were analysed for disease-associated, abnormal prion protein (PrP(BSE)) by using a modified commercial BSE ELISA and a different confirmatory assay. No abnormal prion protein has so far been identified in the cell fraction of milk from cattle incubating BSE by using these methods at their limits of detection.